PERSISTENT ACYLATION OF HIGH-MOLECULAR-WEIGHT PENICILLIN-BINDING PROTEINS BY PENICILLIN INDUCES THE POSTANTIBIOTIC EFFECT IN STREPTOCOCCUS-PYOGENES

Penicillin at 10X MIC induced a postantibiotic effect (PAE) of 2.1 h i n Streptococcus pyogenes. Progressive increases in the densities of pe nicillin-binding proteins (PBPs) 1-3 of the bacterium were detected at 30, 60, and 90 min during the postantibiotic phase. The increase in c olony-forming units during this phase paralleled the kinetics of incor poration of lysine into proteins, suggesting that growth was triggered by de novo synthesis of PBPs. The question was raised as to whether t he progressive increases in densities of PBPs were due to the restorat ion of preexisting PBPs or to synthesis of new PBPs. With 10x MIC of c lindamycin to inhibit PBP synthesis during the postantibiotic phase, t he temporal increase in densities of PBPs 1-3 were totally inhibited. These results suggest that the PAE of penicillin in S. pyogenes is cau sed by irreversible binding of penicillin to PBPs 1-3 and represents t he time necessary for synthesis of new PBPs required for normal growth .